Thymine-DNA glycosylase is part of the DNA-repair machinery. Thymine removal is fastest when it is from a G/T mismatch with a 5'-flanking C/G pair. The glycosylase removes uracil from G/U, C/U, and T/U base pairs faster than it removes thymine from G/T .
Thymine-DNA glycosylase is part of the DNA-repair machinery. Thymine removal is fastest when it is from a G/T mismatch with a 5'-flanking C/G pair. The glycosylase removes uracil from G/U, C/U, and T/U base pairs faster than it removes thymine from G/T [3].
DNA methyltransferase Dnmt3a interacts with TDG. Both the PWWP domain and the catalytic domain of Dnmt3a are able to mediate the interaction with TDG at its N-terminus. The interaction affects the enzymatic activity of both proteins: Dnmt3a positively regulates the glycosylase activity of TDG, while TDG inhibits the methylation activity of Dnmt3a in vitro. Mechanistic link between DNA repair and remethylation at sites affected by methylcytosine deamination
TDG can inhibit expression of smooth muscle-specific genes, at least in part, through disrupting serum response factor/myocardin interactions. The glycosylase activity of TDG is not required for its inhibitory effects on myocardin function. Role for the repair enzyme TDG as a repressor of smooth muscle differentiation via competing with serum response factor for binding to myocardin
TDG has a strong preference for uracil over thymine. TDG is an intriguing protein that, similar to SMUG1, has a low turnover number and strong binding to AP sites. The binding of the glycosylase to the AP site inhibits cleavage by the downstream AP endonuclease
the enzyme repairs a G:T mismatch to G:C, development of a spectrometric assay system for specific and quantitative measurement of intracellular DNA glycosylase activity, overview
DNA methyltransferase Dnmt3a interacts with TDG. Both the PWWP domain and the catalytic domain of Dnmt3a are able to mediate the interaction with TDG at its N-terminus. The interaction affects the enzymatic activity of both proteins: Dnmt3a positively regulates the glycosylase activity of TDG, while TDG inhibits the methylation activity of Dnmt3a in vitro. Mechanistic link between DNA repair and remethylation at sites affected by methylcytosine deamination
TDG can inhibit expression of smooth muscle-specific genes, at least in part, through disrupting serum response factor/myocardin interactions. The glycosylase activity of TDG is not required for its inhibitory effects on myocardin function. Role for the repair enzyme TDG as a repressor of smooth muscle differentiation via competing with serum response factor for binding to myocardin
TDG has a strong preference for uracil over thymine. TDG is an intriguing protein that, similar to SMUG1, has a low turnover number and strong binding to AP sites. The binding of the glycosylase to the AP site inhibits cleavage by the downstream AP endonuclease
TDG transcripts are uniformly and ubiquitously expressed from 7.5 days post-coitum, but are then markedly enriched in specific tissues of the developing fetus. At 14.5 gestational days, TDG is strongly expressed in the developing nervous system, thymus, lung, liver, kidney and intestine. At later stages, high levels of expression were detected in the thymus, brain, nasal epithelium and within proliferating regions of the intestine, skin, kidney, teeth and bone
tumors which overexpress MMTV-v-Ha-ras or MMTV-c-myc transgenes or mice heterozygous for p53 gene disruption, all show elevated TDG and methyl transferase expression specific to the transformed tissue
TDG is strictly cell-cycle regulated. TDG is regulated, opposite to UNG2, EC 3.2.2.27, by displaying the highest expression in the G1-phase and the lowest in the S-phase
opposing roles of CBP/p300 and PKCalpha in regulating the DNA repair functions of TDG, the interplay of acetylation and phosphorylation of TDG in vivo may be critically important in the maintenance of CpG dinucleotides and epigenetic regulation
TDG plays an integral role in CpG maintenance by excising mispaired thymine and uracil in a CpG context and also participates in transcriptional regulation via gene-specific CpG demethylation and functional interactions with the transcription machinery
the enzyme functions in base excision repair and also acts as a key enzyme that participates in active DNA demethylation. Aberrant enzyme expression causes epigenetic modifications and meiotic cell cycle arrest of mouse oocytes
TDG lysines are acetylated by CREB-binding protein, CBP, and p300. Acetylation of the N-terminal region abrogates high-affinity DNA binding and selectively prevents processing of G:T mispairs. TDG acetylation and phosphorylation are mutually exclusive, and their interplay dramatically alters the DNA mispair-processing functions of TDG
protein kinase C alpha interacts with TDG and phosphorylates N-terminal serine residues adjacent to lysines acetylated by CREB-binding protein, CBP, and p300. TDG acetylation and phosphorylation are mutually exclusive, and their interplay dramatically alters the DNA mispair-processing functions of TDG. Phosphorylation does not markedly alter DNA interactions, but may preserve G:T processing in vivo by preventing CBP-mediated acetylation